We have recently found that the DNA proximal to the cellular oncogene locus myc has been rearranged in nearly all mouse myeloma tumors examined, suggesting that this modification may be one of the key events in tumor formation. Preliminary results indicate that a DNA recombination event has replaced the sequences within or near the 5' end of the gene, giving rise to a novel myc mRNA that is shorter than the normal cellular transcript. This oncogene modification will first be analyzed by molecularly cloning the normal and tumor-specific myc genes and identifying the precise site within or near the protein coding regions where the recombination event has occurred. The cloned genes then will be used to determine the DNA sequences that are transcribed into the normal and tumor-specific myc mRNAs using a combination of RNA gel transfer hybridization, electron microscopy of R-loop molecules and S1 nuclease analysis. The biological significance of the DNA rearrangement will be analyzed by assaying the tumor-specific myc RNA for its protein coding ability, by assaying primary myeloma tumors for the same DNA recombination events and by testing the myeloma tumor myc gene for its ability to transform fibroblasts after DNA transfection. From these studies it should be possible to determine how the DNA rearrangement has affected myc gene expression and if the myc gene product has been modified. Myeloma tumors seem to offer a unique opportunity to test if DNA recombinations at oncogene loci are related to the chromosomal translocations observed in the tumors at the cellular level. These studies also will provide an important basis for a more in-depth analysis of changes in the structure of oncogene proteins, rather than their dosage, that are associated with neoplastic transformations.